jm034020y_si_002.chm (5.13 kB)
Benzodiazepines as Potent and Selective Bradykinin B1 Antagonists
datasetposted on 03.04.2003, 00:00 authored by Michael R. Wood, June J. Kim, Wei Han, Bruce D. Dorsey, Carl F. Homnick, Robert M. DiPardo, Scott D. Kuduk, Tanya MacNeil, Kathy L. Murphy, Edward V. Lis, Richard W. Ransom, Gary L. Stump, Joseph J. Lynch, Stacey S. O'Malley, Patricia J. Miller, Tsing-Bau Chen, Charles M. Harrell, Raymond S. L. Chang, Punam Sandhu, Joan D. Ellis, Peter J. Bondiskey, Douglas J. Pettibone, Roger M. Freidinger, Mark G. Bock
Antagonism of the bradykinin B1 receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B1 receptor (Ki = 0.59 nM) and high selectivity against the bradykinin B2 receptor (Ki > 10 μM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent hyperalgesia model.